1. Field of the Invention
The subject invention is concerned with the preparation of derivatives of small haptenic compounds for use in conjugation to antigenic materials to provide antigens which when injected into vertebrates will produce antibodies which have high specificity for the particular haptenic compound. While there are a number of different ways in which a compound may be distinguished from other compounds of similar structure, one of the most versatile and accurate is the use of an antibody which is specific for a specific structure. That is, the binding constant of the antibody with a specific compound is substantially higher than its binding constant with other compounds of similar structure. By using this capability of antibodies, a wide number of different immunoassays have been developed. Among immunoassays which have found commercial acceptance are homogeneous enzyme immumoassays, spin labeled immunoassays, radioimmunoassays, and hemagglutination. Except for the last technique, each of the immunoassays depends upon the competition between the drug to be measured and a drug joined to a detector.
Since the compound of interest will only be modified to prepare the antigen, such modification must take into consideration the effect on the structural specificity of the antibody. That is, in choosing a site of conjugation between the drug and the antigen, it must be chosen so that the resulting product will provide antibodies which will recognize the original drug. Not only must the antibody recognize the original drug, but a significant characteristic of the drug must not be so changed that the antibody will recognize compounds closely related to the drug of interest. In addition, the conjugate of the drug to the antigen should provide high titers for the drug of interest and high binding constants for the drug of interest.
2. Description of the Prior Art
A review article on dibenzazepine compounds may be found in Chemical Reviews, 74, 101 (1974). U.S. Pat. No. 2,948,718 discloses derivatives of dibenzazepine which are reported to have pharmacological properties.